Protective Effects of RIC in Elderly With Acute Ischemic Stroke Complicating Acute Coronary Syndrome (RIC-ACS)

Protective Effects of Remote Ischemic Conditioning in Elderly With Acute Ischemic Stroke Complicating Acute Coronary Syndrome: A Single-center Randomised Controlled Trial

Remote ischemic conditioning (RIC) is a noninvasive strategy in which one or more cycles of brief and transient limb ischemia confers protection against prolonged and severe ischemia in distant organs.This study aimed to investigate whether RIC is safe and effective in patients with AIS complicating ACS

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome; Elderly Patients; Acute Ischemic Stroke
• Intervention / Treatment: Device: RIC; Device: sham-RIC

Detailed Description

Remote ischemic conditioning (RIC) is a noninvasive strategy in which one or more cycles of brief and transient limb ischemia confers protection against prolonged and severe ischemia in distant organs (e.g., brain and heart).It has been demonstrated to be an effective strategy to reduce plasma myocardial enzyme, infarct volume, and incidence of post-ACS heart failure in patients with ACS. Additionally, recent studies have found that RIC was safe and feasible in patients with AIS even in those caused by large artery occlusion and treated with reperfusion therapy, and it might benefit AIS patients by reducing the risk of brain tissue infarction and improving functional outcomes. To date, however, it is still unknow whether RIC, a systematic protective strategy, could benefit patients with AIS complicating ACS.This study aimed to investigate whether RIC is safe and effective in patients with AIS complicating ACS.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Xuanwu Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age≥60yo
• AIS within 24 hours after symptom onset which meet the diagnostic criteria for acute ischemic stroke of the 2013th ASA guidelines, AIS was defined as a clinical episode of neurological dysfunction caused by focal cerebral infarction that can be detected on imaging(e.g.,computed tomography or magnetic resonance imaging of head)
• ACS within 24 hours of stroke onset , and ACS contains ST-segment elevation myocardial infarction, non-ST-elevation myocardial infarction, unstable angina and it was defined when there is a rise and/or fall of plasma cardiac biomarkers (e.g., myocardial enzyme，cardiac troponin I), along with supportive evidence in the form of typical symptoms (e.g., chest pain), suggestive electrocardiographic changes, or imaging evidence of new loss of viable myocardium or new regional wall motion abnormality
• The patients missed the opportunity of or contradicted to reperfusion therapy (i.e., intravenous thrombolysis and endovascular treatments) for both AIS and ACS.
• Informed consent obtained

Exclusion Criteria:

• Unstable vital signs
• Prior ipsilateral stroke with residual deficits
• AIS caused by cardioembolism, suspicious arterial dissection, intracranial sinus thrombolysis, vasculitis, and moyamoya disease.
• Intracranial bleeding.
• Advanced malignancy.
• Uncontrolled hypertension (defined as systolic blood pressure ≥200 mm Hg despite medications at enrollment).
• Any vascular, soft tissue, or orthopedic injury (eg, superficial wounds and fractures of the arm) that contraindicated bilateral arm ischemic preconditioning.
• Peripheral vascular disease that affecting the upper limbs' arteries
• Any disorder that could potentially increase pre-stroke myocardial enzyme concentrations (eg, percutaneous coronary intervention or myocardial infarction within the previous 6 weeks)
• Coronary artery stenosis requiring coronary bypass surgery for the index event within 3 months; or severe heart failure requiring mechanical ventilation or use of an intra-aortic balloon pump
• Taking drugs in the study period or are participating in other clinical trials.
• Severe psychiatric disease.
• Patients who cannot keep treatment or follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: RIC group; Patients with AIS complicating ACS who were eligible for this study received standardized medical treatment and secondary prevention, including antiplatelets, low molecular weight heparin for anticoagulation，statins for lipid-lowering and stabilizing plaque, nitrates for vascular expansion and cardiocerebrovascular risk factors management. Administration of antihypertensive, antidiabetic or other agents were elective at the discretion of the treating physician according to the conditions of the patients. In addition, patients underwent RIC twice daily for 14 days.And the RIC procedure during which bilateral arm cuffs are inflated to a pressure of 200mmHg for five cycles of 5 min followed by 5 min of relaxation of the cuffs.	Device: RIC; The RIC procedure during which bilateral arm cuffs are inflated to a pressure of 200mmHg for five cycles of 5 min followed by 5 min of relaxation of the cuffs.
SHAM_COMPARATOR: sham-RIC group; Patients with AIS complicating ACS who were eligible for this study received standardized medical treatment and secondary prevention, including antiplatelets, low molecular weight heparin for anticoagulation，statins for lipid-lowering and stabilizing plaque, nitrates for vascular expansion and cardiocerebrovascular risk factors management. Administration of antihypertensive, antidiabetic or other agents were elective at the discretion of the treating physician according to the conditions of the patients. In addition, patients underwent sham-RIC twice daily for 14 days.And the sham-RIC procedure during which bilateral arm cuffs are inflated to a pressure of 60mmHg for five cycles of 5 min followed by 5 min of relaxation of the cuffs.	Device: sham-RIC; The sham-RIC procedure during which bilateral arm cuffs are inflated to a pressure of 60mmHg for five cycles of 5 min followed by 5 min of relaxation of the cuffs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiac and cerebrovascular events (MACCEs)	MACCEs defined as all cause of death and recurrence of cardiac and cerebrovascular ischemic events within 3 months after randomization	from baseline to 3 months after therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the proportion of patients achieving functional independence	Functional independence is defined as modified Ranks scale [mRS] ≤2 points	from baseline to 3 months after therapy
the national institutes of health stroke (NIHSS) score	National Institute of Health Stroke Scale (NIHSS) is considered as a standardized assessment of neurological functions in the acute phase of stroke, and it is generally used to quantify patient's neurological impairments on 15 items in 11 fields of different neurological status.The score of the scale ranges from 0 to 42.And higher score indicates worse neurological function.The NHISS will be assessed by certified study investigator, who is blinded to the treatment assignment.	changes from baseline to 7 days, 14 days ,30 days, 90 days after therapy
plasma hypersensitive C-reactive protein（hs-CRP） level	Blood samples were drawn from the cubital vein after enrolling into this study and two weeks after randomization. These samples were centrifuged immediately collection, and serum hs-CRP level were examined in fresh plasma samples.	changes from baseline to 2 weeks after therapy
global registry of acute coronary events (GRACE) score	For each patient, GRACE score was calculated by using specific variables collected at admission. Patients were classified into 3 categories low (1-108), intermediate (109-140), and high (>140), according to the GRACE score	changes from baseline to 7 days, 14 days ,30 days, 90 days after therapy
modified Rankin scale（mRs）	this scale is to evaluate the neurological function，it ranges form 0 to 6, the lower score means better neurological outcome.	changes from baseline to 7 days, 14 days ,30 days, 90 days after therapy

Collaborators and Investigators

• Sponsor: Capital Medical University

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 10, 2019
• Primary Completion (ACTUAL): January 8, 2022
• Study Completion (ACTUAL): April 10, 2022

Study Registration Dates

• First Submitted: March 6, 2019
• First Submitted That Met QC Criteria: March 6, 2019
• First Posted (ACTUAL): March 8, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 29, 2022
• Last Update Submitted That Met QC Criteria: November 24, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: elderly; remote ischemic conditioning; Acute Coronary Syndrome; acute ischemic stroke
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease; Brain Ischemia; Infarction; Brain Infarction; Stroke; Syndrome; Ischemic Stroke; Ischemia; Cerebral Infarction; Acute Coronary Syndrome
• Other Study ID Numbers: RIC-ACS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No